In developmental and disease studies of vertebral motor nerve roots, motor axons and Schwann cells have been extensively studied while the perineurium has been mostly ignored. Because of its juxtaposition to these cell populations, the perineurium is poised to potentially play an integral role in nerve root organogenesis and disease. We have an unprecedented opportunity to elucidate the cell-cell interactions that occur among motor axons, Schwann cells and perineurium by using the zebrafish model system and its unique and powerful combination of in vivo time-lapse imaging and genetics. The overall goal of this application is to uncover the origin of the perineurium and subsequently elucidate the interactions that occur between this cell population and Schwann cells. Through the use of transgenic reporters, morpholino oligonucleotide (MO) technology, pharmacological inhibitors and mutants, we will demonstrate that the perineurium is an essential and integral part of the motor nerve root and plays a role in nerve root organogenesis. Ultimately, by directly implicating the perineurium in nerve root development, research aimed at understanding the cause and progression of many peripheral neuropathies, including Charcot- Marie-Tooth disease, can be expanded to include this structure and lead to a deeper understanding of these disorders. [unreadable] [unreadable]